Method and device for genetic map construction, method and device for haplotype analysis

A device for constructing a high resolution genetic map, comprising:

• a single cell whole genome sequencing unit configured for whole genome sequencing for at least one single cell derived from a human, to obtain whole genome sequencing data of each of the at least one single cells;
• an SNP site genotype statistical unit connected to the single cell whole genome sequencing unit and configured for aligning the whole genome sequencing data of each of the at least one single cell to a reference sequence respectively to determine SNP site genotypes of each of the at least one single cell;
• a parent typing unit connected to the SNP site genotype statistical unit and configured for deducing genotypes of two chromosomes from a male parent and a female parent respectively by means of a maximum parsimony of recombination based on the SNP site genotypes of each of the at least one single cell, to determine male parent a/female parent b typing results of SNP genotype of each of the at least one single cell;
• a linkage region dividing unit connected to the parent typing unit and configured for dividing a chromosome of the species into linkage regions based on the male parent a/female parent b typing results of SNP genotype of each of the at least one single cell, wherein a standard of dividing the chromosome of the species into linkage regions is that:
• (1) the SNP number comprising continuous same a or b is at least 5;
• (2) a physical length of a selected linkage region is greater than 250 kb;
• a recombination rate between contiguous linkage regions calculating unit connected to the linkage region dividing unit and configured for determining a variation ratio of a/b between two continuous linkage regions, to obtain a recombination rate between every two continuous linkage regions for each of the at least one single cells, and determining the recombination map of each of the at least one single cell based on the recombination rate between every two continuous linkage regions, wherein a boundary site between a and b is a recombination site;
• a recombination rate of the recombination site calculating unit connected to the recombination rate between contiguous linkage regions calculating unit and configured for determining a recombination rate of each recombination site to construct the genetic map of the species based on recombination maps of all single cells.

A method of determining a haplotype of a single cell, comprising following steps:

• whole genome sequencing with a first unit the single cell to obtain a whole genome sequencing data of the single cell;
• aligning with a second unit connected to the first unit the obtained whole genome sequencing data to a reference sequence;
• to determine SNP site genotypes of the single cell;
• deducing with a third unit connected to the second unit genotypes of two chromosomes from a male parent and a female parent respectively by means of a maximum parsimony of recombination based on the SNP site genotypes of the single cell to determine male parent a/female parent b typing results of the SNP site genotypes of the single cell;
• dividing with a fourth unit connected to the third unit a chromosome of the species into linkage regions based on the male parent a/female parent b typing results of the SNP site genotypes of the single cell, wherein a standard of dividing the chromosome of the species into linkage regions is that:
• (1) the SNP number comprising continuous same a or b is at least 5;
• (2) a physical length of a selected linkage region is greater than 250 kb;
• determining with a fifth unit the haplotype of the single cell based on the determined linkage region wherein a set of a or b in the same linkage regions of the whole genome constitutes the haplotype of the single cell.

A device for determining a haplotype of a single cell, comprising:

• a single cell whole genome sequencing unit configured for whole genome sequencing the single cell, to obtain a whole genome sequencing data of the single cell;
• an SNP site genotype statistical unit connected to the single cell whole genome sequencing unit and configured for aligning the obtained whole genome sequencing data to a reference sequence, to determine SNP site genotypes of the single cell;
• a parent typing unit connected to the SNP site genotype statistical unit and configured for deducing genotypes of two chromosomes from a male parent and a female parent respectively by means of a maximum parsimony of recombination based on the SNP site genotypes of the single cell, to determine male parent a/female parent b typing results of the SNP site genotypes of the single cell;
• a linkage region (bin) dividing unit connected to the parent typing unit and configured for dividing a chromosome of the species into linkage regions (bin) based on the male parent a/female parent b typing results of the SNP site genotypes of the single cell, wherein a standard of dividing the chromosome of the species into linkage regions is that:
• (1) the SNP number comprising continuous same a or b is at least 5;
• (2) a physical length of a selected linkage region is greater than 250 kb;
• a haplotype determining unit, connected to the linkage region dividing unit and configured for determining the haplotype of the single cell in a determined linkage region, wherein a set of a or b in the same linkage regions of the whole genome constituents the haplotype of the single cell.